(P27-21-26) A Targeted Multi-Fiber Prebiotic Outperforms Single Prebiotic to Reduce Type 1 Diabetes Incidence

Objectives: Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic β‑cell loss, resulting in lifelong insulin therapy dependence. Evidence increasingly shows that the gut microbiota influences T1D risk; for instance, genetically susceptible germ‑free mice show lower incidence of T1D compared to conventional mice. However, it remains unclear whether targeted modulation of the microbiota through prebiotic interventions can reduce T1D incidence. We recently designed a multi‑fiber mixture that enriches complementary beneficial gut taxa, which is more effective than single fibers in modulating community structure and its metabolic activity. We aimed to evaluate the effects of the previously designed fiber mixture and inulin on T1D development.

Methods: Eight-week old female NOD mice were treated with three distinct prebiotic diets: (1) microcrystalline cellulose; (2) the designed fiber mixture; or (3) inulin (n=12-25/group). Fecal samples were collected two days after diet initiation and at endpoint, the onset of diabetes. Blood glucose was monitored weekly, with diabetes defined as >275 mg/dL. Fecal microbiota was assessed via 16S rRNA gene sequencing.

Results: The fiber mixture significantly reduced T1D incidence compared to inulin and cellulose control. Further, all mice fed inulin diet developed diabetes by 18 weeks of age, indicating that inulin may exacerbate disease progression. Analysis of the gut microbiota showed that both the fiber mixture and inulin resulted in beta-diversity shifts two days after prebiotic introduction, with these differences persisting through the study endpoint. Both prebiotic treatments reduced alpha diversity relative to cellulose; however, inulin induced a greater reduction than that of the designed mixture. Further, differential abundance analysis showed that the fiber mixture significantly promoted taxa such as Alistipes and Christensenellaceae R‑7 group. Importantly, these taxa are associated with improved metabolic health.

Conclusions: A designed multi‑fiber prebiotic offers greater protection against T1D than a single-prebiotic approach. Identifying the gut microbial mechanisms underlying this effect may inform gut microbiota‑targeted T1D prevention strategies.

Funding Sources: Supported by the Heartland Children’s Nutrition Collaborative